Secondary sulfonylurea failure: comparison of period until insulin treatment between diabetic patients treated with gliclazide and glibenclamide

We retrospectively evaluated a possible difference in periods until start of insulin treatment between type 2 diabetic patients treated with gliclazide (GCZ) and glibenclamide (GBC), because GCZ might be protective for beta cells than GBC. Subjects were Japanese patients. GCZ group consisted of patients treated with GCZ alone or with GCZ and GBC in the separate treatment periods in combination with or without other oral hypoglycemic agents (OHAs), while GBC group consisted of patients with GBC alone or in combination with other OHAs except GCZ. The periods until the treatment of insulin commenced were calculated using the Kaplan-Meier method. Proportional hazards models were used to adjust the differing variables between GCZ and GBC groups. The periods until the start of insulin treatment from diabetes onset, diabetes treatment, or GCZ or GBC treatment were significantly longer in the GCZ group than those in GBC group (P < 0.001 in each group). Independent variables affecting the period were average HbA1c levels during GCZ or GBC treatment (hazard ratio = 2.5 per %), other OHAs combined (hazard ratio = 1.9 on combination), and difference between GCZ and GBC groups (hazard ratio = 0.5 on GCZ). These results imply that GCZ may be more protective against secondary beta cell failure than GBC.     

瑞格列奈治疗68例2型糖尿病的疗效观察

目的:探讨瑞格列奈治疗2型糖尿病的临床疗效,并评价其安全性。方法:选取2008年10月～2012年7月我院收治的2型糖尿病患者204例,按数字表法随机分为观察组与对照组,各102例。所有患者在严格控制饮食以及运动疗法的基础上,观察组口服瑞格列奈治疗,对照组给予格列齐特。疗程均为12周,12周后比较两组患者的空腹血糖(FPG)、餐后2h血糖(PBG)、糖化血红蛋白(HbA1c)、体重指数(BMI)及不良反应。结果:治疗后观察组和对照组的FPG、HbA1c较治疗前均有显著下降(P<0.05),组间比较差异无统计学意义(P>0.05);与对照组相比,观察组患者的PBG显著下降(P<0.05);两组疗效比较差异无统计学意义(P>0.05)。观察组低血糖反应发生率明显低于对照组,差异具有统计学意义(P<0.05)。结论:采用瑞格列奈治疗2型糖尿病,降血糖疗效显著,且安全可靠,同时具有良好的顺应性,值得临床推广。     

Comparison of Acarbose and Gliclazide as First-line Agents in Patients with Type 2 Diabetes

Summary

Aim: To compare the effect of acarbose and gliclazide on clinical findings, biochemical parameters and safety in type 2 diabetic patients insufficiently controlled with medical nutrition therapy (MNT).

Methods: Seventy-two patients (age 35–70 years, BMI ≤ 35 kg/m²), who had not taken any oral antidiabetic drug previously, were randomised into two groups after a four-week placebo period, and treated for 24 weeks with acarbose (100 mg two to three times daily) and gliclazide (40–80 mg twice daily). The study was open and 57 patients (33 males and 24 females) completed it. MNT was provided for each patient based on personal requirements as defined by a dietitian. The effect of treatment was evaluated by fasting and postprandial (PP) metabolic parameters (blood glucose, insulin and C peptide levels), HbA1C and plasma lipid levels. In addition, side-effects were recorded and clinical examinations performed.

Results: Both drugs were effective in reducing of HbA1C, fasting and PP blood glucose levels. However, PP serum insulin levels in the gliclazide group increased more than those in the group treated with acarbose (p = 0.007). Moreover, a small weight reduction was obtained with acarbose treatment but not with gliclazide. Lipid levels were favourably affected by both drugs. Total cholesterol levels decreased in both groups, the decrease only reaching significance in the acarbose group (p = 0.013). However, serum levels of LDL cholesterol decreased in both groups (acarbose and gliclazide, p = 0.033 and p = 0.023, respectively), but the ratio of HDL to LDL cholesterol increased in the acarbose group only (p = 0.045). Both treatments were generally well tolerated. Common complaints in the acarbose group were flatulence and meteorism (29.6%). However, 10.0% of the patients in the gliclazide group reported at least one mild hypoglycaemic episode.

Conclusions: The results of the study demonstrate that acarbose and gliclazide were reasonably effective in improving metabolic control in patients insufficiently controlled with diet alone, and both treatments were well tolerated. Because of its effects on weight reduction and PP hyperinsulinaemia, acarbose may be preferred as a firstline drug, particularly in the treatment of overweight type 2 diabetic patients.     

胰岛素及格列齐特治疗2型糖尿病大鼠肝脏脂质沉积的机制探讨*

 目的：探讨胰岛素及格列齐特治疗2型糖尿病对大鼠肝脏脂质沉积的影响及机制。方法：制备高脂及链脲佐菌素诱导的2型糖尿病大鼠模型,随机分为糖尿病组、胰岛素组和格列齐特组,并设正常对照组。通过肝脏油红O染色观察其肝细胞脂质沉积情况;ELISA检测血清脂联素水平;实时荧光定量PCR检测肝脏脂联素受体1（AdipoR1）mRNA表达;Western blotting检测肝脏腺苷酸活化蛋白激酶（AMPK）、磷酸化的腺苷酸活化蛋白激酶（Thr172p-AMPK）、固醇调节因子结合蛋白1c（SREBP-1c）、磷酸化的固醇调节因子结合蛋白1c（Ser372p-SREBP1-1c）、乙酰辅酶A羧化酶（ACC）、磷酸化的乙酰辅酶A羧化酶（Ser79p-ACC）和免疫球蛋白结合蛋白（BiP）的表达。结果：糖尿病组肝细胞脂质沉积较正常对照组明显增多,胰岛素和格列齐特治疗后肝细胞脂质沉积明显改善。胰岛素治疗后,血清脂联素的水平及肝脏AdipoR1 mRNA水平较糖尿病组和正常对照组显著升高（P＜0.01）,而格列齐特治疗后两者水平恢复至正常对照组水平。Western blotting结果显示,糖尿病大鼠与正常对照组比较,肝脏Thr172p-AMPK/AMPK和Ser372p-SREBP-1c/SREBP-1c和Ser79p-ACC/ACC表达明显降低（P＜0.01）,BiP表达明显升高（P＜0.01）。胰岛素治疗后,Thr172p-AMPK/AMPK和Ser372p-SREBP-1c/SREBP-1c显著升高（P＜0.01）,Ser79p-ACC/ACC和BiP蛋白表达恢复至正常对照组水平。而格列齐特治疗后Thr172p-AMPK/AMPK和Ser372p-SREBP-1c/SREBP-1c恢复至正常对照组水平,BiP蛋白表达显著下降（P＜0.01）,Ser79p-ACC/ACC与糖尿病组比较无明显改善。结论：胰岛素和格列齐特治疗均能通过激活脂联素-AMPK减轻2型糖尿病大鼠肝脏的脂质沉积。但两者作用的分子机制有所不同。胰岛素激活AMPK,通过抑制SREBP-1c表达、直接磷酸化SREBP-1c抑制SREBP-1c入核等短期和长期的作用以及抑制内质网应激影响SREBP-1c,减少脂质合成;而格列齐特仅通过磷酸化的短期作用和抑制内质网应激对SREBP-1c产生影响,且对脂肪酸氧化无作用。     

老年糖尿病住院患者药疗方案的成本-效果分析

目的：评价老年糖尿病住院患者不同药物治疗方式中不同用药方案所产生的经济结果。方法：运用成本-效果分析法分别对口服降糖药物治疗和应用胰岛素治疗两种治疗方式中各3种主要的用药方案进行分析评价。结果：格列齐特、二甲双胍联合用药是口服抗糖尿病药物治疗方式中的较优方案；格列齐特、阿卡波糖、胰岛素联合用药是应用胰岛素的药物治疗方式中的较优方案。结论：运用药物经济学理论指导临床合理用药，可使有限的资源得到合理配置。     

格列齐特治疗2型糖尿病的临床疗效观察

目的 对格列齐特缓释片治疗初发2型糖尿病患者的临床疗效进行观察.方法 将118例初发2型糖尿病患者随机分为三组,分别应用格列齐特缓释片、瑞格列奈(进121)、重组人胰岛素治疗12周,测定三组受试者治疗前后的糖化血红蛋白、空腹及餐后2 h血糖,并观察低血糖事件,对测试结果进行比较.结果 格列齐特缓释片治疗组空腹和餐后2 h血糖水平与重组人胰岛素治疗组差异无统计学意义(P>0.05).格列齐特缓释片治疗组空腹血糖控制优于瑞格列奈(进口)治疗组(P<0.01).重组人胰岛素对空腹血糖的控制优于瑞格列奈(进口)组(P<0.01),但两组间餐后血糖水平无明显差异.结论 对空腹血糖、餐后2 h血糖及糖化血红蛋白的控制,格列齐特缓释片、重组人胰岛素、瑞格列奈(进口)均有较好疗效.     

利用六通道光纤传感系统实时监测格列齐特片Ⅱ的体外溶出度

目的利用六通道光纤药物溶出度测定仪,建立实时、在位监测格列齐特片Ⅱ体外溶出度的测定方法,并比较测定不同厂家共7批格列齐特片Ⅱ的体外溶出参数。方法采用FODT-601检测了格列齐特片Ⅱ的溶出度,并与《中国药典》药品标准溶出度测定结果进行了比较,无显著性差异（P〉0．05）。溶出度测定条件为：测定波长240nm、基线校正波长290nm、温度37℃、转速150r!min、数据采集间隔120s、监测时间180min、溶出介质为磷酸盐缓冲液pH（8．60±0．05）、溶出体积1000ml、转篮法、光纤探头2mm。结果共测定了两个厂家不同批次的格列齐特片Ⅱ在60、180min的溶出度及溶出曲线,其中一个厂家的格列齐特片Ⅱ符合《中国药典》规定,另一个厂家的格列齐特片Ⅱ在180min的溶出度不符合《中国药典》规定。两个厂家的格列齐特片Ⅱ溶出曲线存在非常显著性差异。结论光纤药物溶出度实时测定仪原位、准确、连续、定量地反映了药物的溶出过程,可比较出不同厂家之间同种药品的溶出过程差异。     

非胰岛素依赖型糖尿病人接受不同降糖药物治疗对血浆血栓素B_2与6-酮-前列腺素F_(1α)水平的影响

本文报告114例不同降糖药物治疗的非胰岛素依赖型糖尿病患者血浆TXA_2和PGI_2的稳定代谢物TXB_2与6-酮-PGF_(1α)及血脂等测定结果。使用胰岛素组6-酮-PGF_(12)水平显著高于优降糖或优降糖 降糖灵组;HDLch与HDL2ch也较后两组高。25例口服降糖药者改用甲磺吡脲3个月后6-酮-PGF_(12)水平显著上升,TXB_2改变相反,血脂异常也得改善。结果提示胰岛素或甲磺吡脲治疗可能有助于纠正前列腺素平衡失调。     

Preparation and Crystallographic Analysis of Gliclazide Polymorphs

Since the introduction of gliclazide in the pharmaceutical industry, a large number of research groups have been engaged in various investigations aiming to enhance its biomedical application. But, very limited efforts have been made to study polymorphism of gliclazide. Therefore, this study focuses on solvent-induced polymorphism of gliclazide and its characterization by thermal methods. Three polymorphs namely, Form-I, II and III and an amorphous powder were produced from different solvents and solvent mixtures. Crystals were analyzed using infrared spectroscopy, differential scanning calorimetry, X-ray powder diffraction and single crystal x-ray diffraction. Polymorph Form-I is found to exist in centro-symmetric triclinic P-1 space group and has endothermic peak at 162.93°. Form-II has endothermic peak from 171.2° to 172.35° and exists in centro-symmetric monoclinic P2₁/a space group while Form-III has endothermic peak from 168.93° to 169.86° and exists in centro-symmetric monoclinic P2₁/n space group. The equilibrium solubility values of Form-I, II, III and the amorphous form were 0.4825±0.025, 0.2341±0.042, 0.2581±0.038 and 0.5213±0.072 mg/ml, respectively. The Form-I has relatively higher solubility and similar to that of amorphous gliclazide. Form-II and Form-III are relatively most stable and least soluble. However, there was no remarkable difference in their aqueous solubility under the conditions in which study was conducted.     

Pioglitazone elicits long-term improvements in insulin sensitivity in patients with type 2 diabetes: comparisons with gliclazide-based regimens

Aims/hypothesis Recent studies have demonstrated that pioglitazone (PIO) has beneficial effects on insulin sensitivity compared with placebo in patients with type 2 diabetes. The effects of PIO and gliclazide (GLIC)-based therapy on insulin sensitivity have not previously been directly compared. This analysis aimed to compare the effects of 52 weeks of treatment with PIO (30–45 mg/day) and GLIC (80–320 mg/day), both titrated to maximum tolerable doses, as monotherapy or in combination with metformin (MET), on insulin sensitivity and lipid parameters known to be related to insulin sensitivity in patients with type 2 diabetes.Methods We performed an analysis of 1,880 patients with inadequately controlled type 2 diabetes (HbA₁c 7.5–11.0%) who were participants in two parallel-group, double-blind, double-dummy, randomised, multicentre, clinical trials. Measures of insulin sensitivity and lipids were assessed.Results The PIO- and GLIC-based regimens produced similar levels of glycaemic control (HbA₁c). In both trials, insulin sensitivity as assessed using the homeostasis model assessment was improved in patients receiving PIO, but decreased in those receiving GLIC (mean change, baseline to endpoint: PIO 15.5, GLIC –15.6; p<0.001 and PIO+MET 18.9, GLIC+MET –5.3; p<0.001). Improvements in the atherogenic index of plasma (mean change: PIO –0.17, GLIC –0.08; p<0.001 and PIO+MET –0.17, GLIC+MET –0.02; p<0.001), triglycerides (mean change, mmol/l: PIO+MET –0.62, GLIC+MET –0.22; p<0.001) and NEFA (mean change, mmol/l: PIO+MET –0.12, GLIC+MET–0.05; p<0.001) were greater in PIO-treated patients than in patients receiving GLIC.Conclusions/interpretation The PIO-based regimens resulted in improved insulin sensitivity and more favourable insulin sensitivity-related lipid profiles compared with the GLIC-based regimens. These benefits may be important in the management of cardiovascular risk in patients with type 2 diabetes.